It is currently held that lymphocytes are involved in the tissue and bone destruction associated with chronic periodontal disease in humans; however, the actual mechanism of interactions between lymphocytes and gingival fibroblasts which lead to this destruction are not known. The presence of a preponderance of bone marrow-derived (B) lymphocytes has been found in these lesions, and recent work has shown that peripheral blood B lymphocytes can be activated in vitro by binding of agents to their Fc and C3 receptors. These activated B lymphocytes produce lymphokines, including lymphotoxin which destroys gingival fibroblasts. It is thought that B lymphocytes may be thus activated in vivo. This project proposal outlines studies for comparing the reactivities of peripheral blood lymphocytes and those isolated from gingival tissue in relation to gingival fibroblast destruction. This will be done using cytotoxicity assays with gingival fibroblast cultures. In addition, various means of activating B lymphocytes and amplifying their responses will be explored. Activating agents include antigen-antibody complexes prepared with antisera to dental plaque and oral bacteria, complement-binding agents, and soluble factors from activated cells. The final phase of the program will focus on collagen synthesis and secretion by gingival fibroblasts in contact with lymphocyte populations to assess whether there may be impairment of these functions. It is hoped that these studies of the consequences of interaction of the immune system with gingival fibroblasts in chronic periodontitis may give us an indication of the mechanisms involved in tissue destruction and may lead to ways of preventing or retarding this process in human periodontal disease.